title: Reversal of deficits in dendritic spines, BDNF and Arc expression in the amygdala during alcohol dependence by HDAC inhibitor treatment.
abstract: Development of anxiety-like behaviours during ethanol withdrawal has been correlated with increased histone deacetylase (HDAC) activity and decreased brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc) gene expression in the amygdala. Furthermore, HDAC-mediated histone modifications play a role in synaptic plasticity. In this study we used the HDAC inhibitor trichostatin A (TSA) to determine whether HDAC inhibition could prevent ethanol withdrawal-induced deficits in dendritic spine density (DSD), BDNF or Arc expression in the amygdala of rats. It was found that decreased BDNF and Arc expression in the central (CeA) and medial nucleus of amygdala (MeA), observed during withdrawal after chronic ethanol exposure, were normalized following acute TSA treatment. TSA treatment was also able to attenuate anxiety-like behaviours during ethanol withdrawal and correct the observed decrease in DSD in the CeA and MeA of ethanol-withdrawn rats. Taken together, these findings demonstrate that correcting the deficits in histone acetylation through TSA treatment also amends downstream synaptic plasticity-related deficits such as BDNF and Arc expression, and DSD in the CeA and MeA as well as attenuates anxiety-like behaviours in rats during withdrawal after chronic ethanol exposure.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Huaibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Amul J
authors.initials: AJ
authors.lastname: Sakharkar
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Teppen
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Pandey
mesh_terms: D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D056572:Histone Deacetylase Inhibitors; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein